U.S. Pat. No. 5,162,430, issued Nov. 10, 1992 to Rhee et al., and commonly owned by the assignee of the present application, discloses collagen-synthetic polymer conjugates and methods of covalently binding collagen to synthetic hydrophilic polymers. Commonly owned U.S. Pat. No. 5,328,955, issued Jul. 12, 1994 to Rhee et al., discloses various activated forms of polyethylene glycol and various linkages which can be used to produce collagen-synthetic polymer conjugates having a range of physical and chemical properties. Commonly owned U.S. Pat. No. 5,324,775, issued Jun. 28, 1994 to Rhee et al., discloses biocompatible polymer conjugates prepared by covalently binding biologically inert, biocompatible polymers to synthetic hydrophilic polymers.
Commonly owned U.S. Pat. No. 5,510,418, issued Apr. 23, 1996, discloses conjugates comprising various species of glycosaminoglycans covalently bound to synthetic hydrophilic polymers, which are optionally bound to collagen as well. Commonly owned U.S. Pat. No. 5,565,519, issued Oct. 15, 1996, discloses collagen-polymer conjugates comprising chemically modified collagens such as, for example, succinylated collagen or methylated collagen, covalently bound to synthetic hydrophilic polymers to produce optically clear materials for use in ophthalmic or other medical applications.
Hydrophobic crosslinking agents such as disuccinimidyl suberate, bis(sulfosuccinimidyl)suberate, and dithiobis(succinimidyl)propionate have a long history of use for crosslinking biologically active peptides, as described in the 1992 Pierce (Rockford, Ill.) catalog.
All publications cited above and herein are incorporated herein by reference to describe and disclose the subject matter for which it is cited.
We now disclose a detailed description of preferred embodiments of the present invention, including crosslinked biomaterial compositions prepared using various hydrophobic crosslinking agents and crosslinked biomaterial compositions prepared using mixtures of hydrophobic and hydrophilic crosslinking agents.